TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16411	49456;49457;49458	chr2:178614166;178614165;178614164	chr2:179478893;179478892;179478891
N2AB	14770	44533;44534;44535	chr2:178614166;178614165;178614164	chr2:179478893;179478892;179478891
N2A	13843	41752;41753;41754	chr2:178614166;178614165;178614164	chr2:179478893;179478892;179478891
N2B	7346	22261;22262;22263	chr2:178614166;178614165;178614164	chr2:179478893;179478892;179478891
Novex-1	7471	22636;22637;22638	chr2:178614166;178614165;178614164	chr2:179478893;179478892;179478891
Novex-2	7538	22837;22838;22839	chr2:178614166;178614165;178614164	chr2:179478893;179478892;179478891
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-6
• Domain position: 61
• Structural Position: 92
• Q(SASA): 0.4423
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
K/R	None	None	0.003	N	0.203	0.068	0.269558022972	gnomAD-4.0.0	1.59395E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86197E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
K/A	0.6	likely_pathogenic	0.6632	pathogenic	-0.498	Destabilizing	0.404	N	0.646	neutral	None	None	None	None	N
K/C	0.7398	likely_pathogenic	0.7724	pathogenic	-0.571	Destabilizing	0.991	D	0.793	deleterious	None	None	None	None	N
K/D	0.8767	likely_pathogenic	0.9007	pathogenic	0.2	Stabilizing	0.826	D	0.672	neutral	None	None	None	None	N
K/E	0.3653	ambiguous	0.4479	ambiguous	0.29	Stabilizing	0.338	N	0.609	neutral	N	0.47413498	None	None	N
K/F	0.82	likely_pathogenic	0.8514	pathogenic	-0.365	Destabilizing	0.967	D	0.765	deleterious	None	None	None	None	N
K/G	0.8215	likely_pathogenic	0.8406	pathogenic	-0.812	Destabilizing	0.575	D	0.659	neutral	None	None	None	None	N
K/H	0.3314	likely_benign	0.3469	ambiguous	-1.04	Destabilizing	0.826	D	0.721	prob.delet.	None	None	None	None	N
K/I	0.3736	ambiguous	0.4481	ambiguous	0.288	Stabilizing	0.906	D	0.767	deleterious	None	None	None	None	N
K/L	0.396	ambiguous	0.439	ambiguous	0.288	Stabilizing	0.575	D	0.659	neutral	None	None	None	None	N
K/M	0.3235	likely_benign	0.386	ambiguous	0.086	Stabilizing	0.965	D	0.714	prob.delet.	D	0.524630648	None	None	N
K/N	0.7403	likely_pathogenic	0.7906	pathogenic	-0.273	Destabilizing	0.782	D	0.593	neutral	N	0.477117039	None	None	N
K/P	0.8196	likely_pathogenic	0.8531	pathogenic	0.056	Stabilizing	0.906	D	0.723	prob.delet.	None	None	None	None	N
K/Q	0.1959	likely_benign	0.2284	benign	-0.336	Destabilizing	0.003	N	0.358	neutral	N	0.497874196	None	None	N
K/R	0.0823	likely_benign	0.0771	benign	-0.362	Destabilizing	0.003	N	0.203	neutral	N	0.451456569	None	None	N
K/S	0.6903	likely_pathogenic	0.7485	pathogenic	-0.946	Destabilizing	0.404	N	0.563	neutral	None	None	None	None	N
K/T	0.2865	likely_benign	0.3655	ambiguous	-0.654	Destabilizing	0.505	D	0.653	neutral	N	0.415209907	None	None	N
K/V	0.3527	ambiguous	0.4189	ambiguous	0.056	Stabilizing	0.826	D	0.695	prob.neutral	None	None	None	None	N
K/W	0.7631	likely_pathogenic	0.7702	pathogenic	-0.256	Destabilizing	0.991	D	0.778	deleterious	None	None	None	None	N
K/Y	0.6849	likely_pathogenic	0.7148	pathogenic	0.042	Stabilizing	0.906	D	0.764	deleterious	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.